Submissions for variant NM_001382567.1(STIM1):c.92C>T (p.Ala31Val)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002966551	SCV003279790	uncertain significance	Stormorken syndrome; Combined immunodeficiency due to STIM1 deficiency; Myopathy with tubular aggregates	2022-04-24	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs778297119, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 31 of the STIM1 protein (p.Ala31Val). This variant has not been reported in the literature in individuals affected with STIM1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics	RCV003170723	SCV003914469	uncertain significance	Inborn genetic diseases	2023-03-06	criteria provided, single submitter	clinical testing	The c.92C>T (p.A31V) alteration is located in exon 1 (coding exon 1) of the STIM1 gene. This alteration results from a C to T substitution at nucleotide position 92, causing the alanine (A) at amino acid position 31 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004690339	SCV005185374	uncertain significance	not specified	2024-05-07	criteria provided, single submitter	clinical testing	Variant summary: STIM1 c.92C>T (p.Ala31Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251338 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.92C>T in individuals affected with STIM1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2067637). Based on the evidence outlined above, the variant was classified as uncertain significance.