Submissions for variant NM_001386795.1(DTNA):c.955A>G (p.Met319Val)

gnomAD frequency: 0.00046  dbSNP: rs141981161

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171930	SCV000054853	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083773	SCV000642428	likely benign	Left ventricular noncompaction 1	2025-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000171930	SCV000717357	likely benign	not provided	2021-02-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23861362)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000606031	SCV000966424	likely benign	not specified	2018-10-24	criteria provided, single submitter	clinical testing	The p.Met319Val variant in DTNA is classified as likely benign because it has be en identified in 0.15% (38/24960) of African chromosomes by gnomAD (http://gnoma d.broadinstitute.org). ACMG/AMP Criteria applied: BS1
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000606031	SCV001363629	likely benign	not specified	2019-11-18	criteria provided, single submitter	clinical testing	Variant summary: DTNA c.955A>G (p.Met319Val) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00013 in 251432 control chromosomes, predominantly at a frequency of 0.0018 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 72 fold of the estimated maximal expected allele frequency for a pathogenic variant in DTNA causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.955A>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004751325	SCV005346659	uncertain significance	DTNA-related disorder	2024-07-10	no assertion criteria provided	clinical testing	The DTNA c.1A>G variant is predicted to disrupt the translation initiation site (Start loss). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.15% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.