Submissions for variant NM_004393.6(DAG1):c.212C>A (p.Thr71Lys)

dbSNP: rs142572135

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000698659	SCV000827339	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2P; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 71 of the DAG1 protein (p.Thr71Lys). This variant is present in population databases (rs142572135, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with DAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 576217). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DAG1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Eurofins Ntd Llc (ga)	RCV000730056	SCV000857765	uncertain significance	not provided	2017-10-27	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000730056	SCV002770794	uncertain significance	not provided	2021-06-09	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000730056	SCV003834230	uncertain significance	not provided	2021-02-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004026453	SCV004852965	uncertain significance	Inborn genetic diseases	2023-11-17	criteria provided, single submitter	clinical testing	The c.212C>A (p.T71K) alteration is located in exon 2 (coding exon 1) of the DAG1 gene. This alteration results from a C to A substitution at nucleotide position 212, causing the threonine (T) at amino acid position 71 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004586886	SCV005076124	uncertain significance	not specified	2024-04-16	criteria provided, single submitter	clinical testing	Variant summary: DAG1 c.212C>A (p.Thr71Lys) results in a non-conservative amino acid change located in the Dystroglycan-type cadherin-like (IPR006644) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.6e-05 in 251296 control chromosomes. To our knowledge, no occurrence of c.212C>A in individuals affected with DAG1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 576217). Based on the evidence outlined above, the variant was classified as uncertain significance.